反应详情

N-[2-((R)-6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl]-2-hydroxy-acetamide (20 mg) was dissolved in absolute THF (2 ml), and reacted at room temperature with sodium hexamethyldisilazide solution (0.5 ml; 2 M in THF) with stirring. Afterward, 1,1-carbonyldiimidazole (13 mg) was added and the mixture was stirred at room temperature for 2 h. After standing overnight, the reaction mixture was concentrated, the residue was dissolved in ethyl acetate/water and basified with sodium hydrogencarbonate solution, and the phases were separated. The aqueous phase was extracted three times with ethyl acetate. The combined extracts were dried with magnesium sulfate, filtered and concentrated. The residue was purified by means of preparative HPLC. The fractions comprising product were combined, the acetonitrile was removed on a rotary evaporator, and the aqueous residue was neutralized with saturated sodium hydrogencarbonate solution and extracted three times with ethyl acetate. After the combined ethyl acetate phases had been dried over magnesium sulfate, they were filtered and concentrated to dryness. The residue was dissolved in water/acetonitrile and the clear solution was freeze-dried overnight. 10 mg of the desired product were obtained.

1. stirringthe mixture was stirred at room temperature for 2 h
2. concentrationthe reaction mixture was concentrated
3. dissolutionthe residue was dissolved in ethyl acetate/water
4. customthe phases were separated
5. extractionThe aqueous phase was extracted three times with ethyl acetate
6. dry with materialThe combined extracts were dried with magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was purified by means of preparative HPLC
10. customthe acetonitrile was removed on a rotary evaporator
11. extractionextracted three times with ethyl acetate
12. dry with materialAfter the combined ethyl acetate phases had been dried over magnesium sulfate, they
13. filtrationwere filtered
14. concentrationconcentrated to dryness
15. dissolutionThe residue was dissolved in water/acetonitrile
16. customthe clear solution was freeze-dried overnight